standing on the shoulders of giants, german demidov,...
TRANSCRIPT
![Page 1: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/1.jpg)
Standing on the
shoulders of giants,
German Demidov,
Bioinformatics
Summer School
2017
![Page 2: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/2.jpg)
BiologyandBigData
> Discoveringtruth
bybuildingon
previous
discoveries
![Page 3: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/3.jpg)
Whyitisuseful?
Justoneexample:
![Page 4: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/4.jpg)
Usingdatafromconsortia
> Whichtypesofdatacanyouobtainfrom
consortia?Howtoaccessanddownload
data?
> Howtoworkasapartofconsortia?Which
problemsyoumayface?
![Page 5: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/5.jpg)
ImportantRemark
> Workshops“Howtouseconsortium_name”
usuallytake~3days(ie
https://www.encodeproject.org/tutorials/
encode-meeting-2016/),wewilltrytomake
anoverviewin1hour
> However,ifyouwanttofindmoreinformation
– google“consortium_nameworkshop”
> Thereareseparatepapers(i.e.EwanBirney,
2012,Nature,aboutENCODE)
![Page 6: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/6.jpg)
GWASConsortia
> http://
www.wikigenes.org/
e/art/e/185.html
> 500.000genotyped
peopleinUK
![Page 7: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/7.jpg)
EWASConsortia
![Page 8: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/8.jpg)
GenomicsConsortia
> TheExomeAggregationConsortium
> 1000Genomes
> HumanReferenceGenome
> InternationalCancerGenomeConsortium
> TheCancerGenomeAtlas
> PanCancerAnalysisofWholeGenomes
> GTEx
![Page 9: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/9.jpg)
EpigenomicsConsortia
> ENCODE
> RoadmapEpigenomics
> BluePrint
> InternationalHumanEpigenome
Consortium
![Page 10: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/10.jpg)
ExACOverivew
> http://exac.broadinstitute.org/about
> Firstthingtodo–lookandreadflagship
paper!
> Thedatasetprovidedonthiswebsitespans
60,706unrelatedindividualssequencedas
partofvariousdisease-specificand
populationgeneticstudies.
![Page 11: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/11.jpg)
ExAC:Whyitisuseful
Itisusedto
> calculateobjectivemetricsofpathogenicityforsequencevariants,
> identifygenessubjecttostrongselectionagainstvariousclassesofmutation;identifying3,230geneswithnear-completereductionofnumberofpredictedprotein-truncatingvariants,with72%ofthesegeneshavingnocurrentlyestablishedhumandiseasephenotype,
> efficientfilteringofcandidatedisease-causingvariants
![Page 12: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/12.jpg)
ExAC:Results
• ANNOVARandATAVwereupdatedusing
ExACdata
• CADDscoreswerere-calculated
• CommercialtoolssuchasGoldenHelixand
GeneTalkalsoincorporatedExACdata
![Page 13: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/13.jpg)
ExAC:Download
> Download
![Page 14: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/14.jpg)
ExAC:Methods
> FlagshipPaper–Methods–short
descriptionwithdetailedpipelinesin
SupplementaryInformation
> 91,796individualexomesdrawnfroma
widerangeofprimarilydisease-focused
consortia
![Page 15: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/15.jpg)
ExACQualityAssesment
> Comparisonwithintrios:singletontransmissionrateof50.1%(~50%)
> >10.000sampleswerecheckedwithSNPArrays–97-99%heterozygousconcordance
> Platinumstandardgenomesequencedwith5differenttechnologies–99.8%Sensitivity,0.056%FDR
> Comparisonwith13WGS~30x,PCR-free
> IndelFDRishigher(4.7%),singletonvariantsshowhigherFDR
> FDRisdifferentfordifferentannotationclasses(missense,synonymous,proteintruncating)
![Page 16: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/16.jpg)
ExACSampleFiltering
> Only60.706samplespassedQCoutof91.796
> SetofcommonSNPswasselected(5.400)andsampleswithoutlierheterozygositywereremovedpriortoPCA
> Persamplenumberofvariants,transition/transversion(TiTv)ratio,alternatealleleheterozygous/homozygous(Het/Hom)ratioandinsertion/deletion(indel)ratio
> Closerelativeswereremoved
> Finalcoverage:80%oftargetedbases>20x
> 77%wereenrichedwithAgilentKit(33MBtarget)
![Page 17: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/17.jpg)
1000GP
> http://www.internationalgenome.org
![Page 18: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/18.jpg)
1000GP:Overview,goals
> http://www.internationalgenome.org/data-portal/sample
> Prettyconvenientdataportalthatallowsyounicefiltering!
> Thegoalofthe1000GenomesProjectwastofindmostgeneticvariantswithfrequenciesofatleast1%inthepopulationsstudied.
> Theprojectplannedtosequenceeachsampleto4xgenomecoverage;atthisdepth,sequencingcannotdiscoverallvariantsineachsample,butcanallowthedetectionofmostvariantswithfrequenciesaslowas1%.
![Page 19: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/19.jpg)
1000GP:MainPublications
> Pilot:Amapofhumangenomevariationfrompopulation-scalesequencingNature467,1061–1073(28October2010)
> Phase1:Anintegratedmapofgeneticvariationfrom1,092humangenomesNature491,56–65(01November2012)
> Phase3:AglobalreferenceforhumangeneticvariationNature526,68–74(01October2015)
> Anintegratedmapofstructuralvariationin2,504humangenomesNature526,75–81(01October2015)
![Page 20: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/20.jpg)
1000GP:Pipeline
![Page 21: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/21.jpg)
1000GP:PowerofDetection,Heterozygous
Discordance,SequencingDepth
![Page 22: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/22.jpg)
1000GP:Results
![Page 23: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/23.jpg)
1000GP:VariantCalling
![Page 24: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/24.jpg)
1000GP:CNVs
![Page 25: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/25.jpg)
1000GP:CNVsconcordance
![Page 26: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/26.jpg)
PanCancerAnalysisOfWG
> https://dcc.icgc.org/pcawg
![Page 27: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/27.jpg)
PanCancerAnalysisOfWG
1. Novelsomaticmutationcallingmethods
2. Analysisofmutationsinregulatoryregions
3. Integrationofthetranscriptomeandgenome
4. Integrationoftheepigenomeandgenome
5. Consequencesofsomaticmutationsonpathwayandnetworkactivity
6. Patternsofstructuralvariations,signatures,genomiccorrelations,retrotransposonsandmobileelements
7. Mutationsignaturesandprocesses
8. Germlinecancergenome
9. Inferringdrivermutationsandidentifyingcancergenesandpathways
10. Translatingcancergenomestotheclinic
11. Evolutionandheterogeneity
12. Portals,visualizationandsoftwareinfrastructure
13. Molecularsubtypesandclassification
14. Analysisofmutationsinnon-codingRNA
15. Mitochondrial
16. Pathogens
![Page 28: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/28.jpg)
PCAWG,WG8:Validation
> High-coveragevalidation
> 3maincallers:BroadInstitute–HaplotypeCaller,Annai-RTG(privatecompany),Freebayes(EMBL-DKFZ)
> 50samples,5000sitespersamplesequencedwith~1000depth
> ~2300SNVs,~2700indels
> SNPRecall/PPV/concordance~0.995
> Indels:0.94Recall,0.91PPV,concordance0.88
![Page 29: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/29.jpg)
PCAWGWG8,CNVs
> CNVs
![Page 30: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/30.jpg)
PCAWGWG8:Results
> Sensitivity,deletionsonly~60%,
duplications~40%!
![Page 31: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/31.jpg)
FurtherInformation
> Flagshippaperisnotinformative:/
> 16papersarereleasedinbioRxiv
![Page 32: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/32.jpg)
GTEx
> TheGenotype-TissueExpressionprojectaimstoprovidetothescientificcommunityaresourcewithwhichtostudyhumangeneexpressionandregulationanditsrelationshiptogeneticvariation
> Variationsingeneexpressionthatarehighlycorrelatedwithgeneticvariationcanbeidentifiedasexpressionquantitativetraitloci,oreQTLs
![Page 33: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/33.jpg)
GTEx
> Alotofgeneticchangesassociatedwithcommonhumandiseases,suchasheartdisease,cancer,diabetes,asthma,andstroke,liesoutsideoftheprotein-codingregionsofgenes
> ThecomprehensiveidentificationofhumaneQTLswillgreatlyhelptoidentifygeneswhoseexpressionisaffectedbygeneticvariation
![Page 34: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/34.jpg)
GTExDataOverview
![Page 35: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/35.jpg)
GTExScheme
![Page 36: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/36.jpg)
GTEx:CausesofDeath
![Page 37: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/37.jpg)
ENCODE:Overview
> https://www.encodeproject.org
> EncyclopediaofDNAelements
> ThegoalofENCODEistobuilda
comprehensivepartslistoffunctional
elementsinthehuman(mouse/fly/worm)
genome
![Page 38: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/38.jpg)
ENCODETimeline
![Page 39: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/39.jpg)
ENCODEasfor2012
![Page 40: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/40.jpg)
ENCODE:TypesofData
> https://www.encodeproject.org
![Page 41: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/41.jpg)
ENCODE:DataMatrix
![Page 42: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/42.jpg)
ENCODE:AuditCategory
Eachsamplecanhavemultiple
QCissuesandcanstill
Beavailablefordownloading!
![Page 43: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/43.jpg)
ENCODE:ResultofAnalysis
![Page 44: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/44.jpg)
ENCODE:GroundLevel
![Page 45: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/45.jpg)
ENCODE:Mid-level
![Page 46: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/46.jpg)
ENCODE:Top-Level
![Page 47: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/47.jpg)
ENCODEpublications
> Ofcourse,oneoftheproductsis
publicaitons!
0
100
200
300
400
500
600
Nu
mb
er
of
Pu
blic
ati
on
s
Cumulative ENCODE Publications Over Time
Papers from Non-ENCODE Authors
Papers from ENCODE 2 Production Groups
![Page 48: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/48.jpg)
ENCODEstandards
> DataStandards
![Page 49: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/49.jpg)
BluePrint
> “BLUEPRINTisalarge-scaleresearchprojectreceivingcloseto30millioneurofundingfromtheEU.”
> 42leadingEuropeanscientificcenters
> Theaimtofurthertheunderstandingofhowgenesareactivatedorrepressedinbothhealthyanddiseasedhumancells
> Focusondistincttypesofhaematopoieticcellsfromhealthyindividualsandontheirmalignantleukaemiccounterparts
![Page 50: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/50.jpg)
BluePrint
> http://www.blueprint-epigenome.eu
> Publications(CellPapers)&DataPortal
![Page 51: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/51.jpg)
BluePrint
> http://dcc.blueprint-epigenome.eu/#/home
![Page 52: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/52.jpg)
BluePrint
![Page 53: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/53.jpg)
BluePrint
![Page 54: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/54.jpg)
RoadMapEpigenomics
> TheNIHRoadmapEpigenomicsResearchtotransformourunderstandingofhowepigeneticscontributestodisease
> TheConsortiumleveragesexperimentalpipelinesbuiltaroundnext-generationsequencingtechnologiestomapDNAmethylation,histonemodifications,chromatinaccessibilityandsmallRNAtranscriptsinstemcellsandprimaryexvivotissuesselectedtorepresentthenormalcounterpartsoftissuesandorgansystemsfrequentlyinvolvedinhumandisease
![Page 55: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/55.jpg)
RoadMapEpigenomics
![Page 56: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/56.jpg)
RoadMapEpigenomics
![Page 57: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/57.jpg)
RoadMapEpigenomics
ItlookslikewecangetProtocolsclickingonthelink,however,
therearenotalotofthemthere.Theprotocolsaresuper
outdated!(egREMCSTANDARDSANDGUIDELINESFORCHIP-
SEQDEC.2,2011—V1.0)
![Page 58: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/58.jpg)
RoadMapEpigenomics
> Ifyouwannatoworkwiththesedata–readthepaper“Integrativeanalysisof111referencehumanepigenomes”(+16ENCODE2012,donotprintthepaper!)
> Gothroughthe“Publications”list
![Page 59: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/59.jpg)
RoadMapEpigenomics
ThemostusefulsectionisMethods:
> RNA-sequniformprocessingandquantificationforconsolidatedepigenomes
> ChIP-seqandDNase-sequniformreprocessingforconsolidatedepigenomes
> Methylationdatacross-assaystandardizationanduniformprocessingforconsolidatedepigenomes
> Chromatinstatelearning
> Etc.
![Page 60: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/60.jpg)
RoadMapEpigenomics
> Publications
![Page 61: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/61.jpg)
RoadMapEpigenomics
> HistonemarkcombinationsshowdistinctlevelsofDNAmethylationandaccessibility,andpredictdifferencesinRNAexpressionlevelsthatarenotreflectedineitheraccessibilityormethylation.
> Megabase-scaleregionswithdistinctepigenomicsignaturesshowstrongdifferencesinactivity,genedensityandnuclearlaminaassociations,suggestingdistinctchromosomaldomains.
> Approximately5%ofeachreferenceepigenomeshowsenhancerandpromotersignatures,whicharetwofoldenrichedforevolutionarilyconservednon-exonicelementsonaverage.
> Epigenomicdatasetscanbeimputedathighresolutionfromexistingdata,completingmissingmarksinadditionalcelltypes,andprovidingamorerobustsignalevenforobserveddatasets.
> Dynamicsofepigenomicmarksintheirrelevantchromatinstatesallowadata-drivenapproachtolearnbiologicallymeaningfulrelationshipsbetweencelltypes,tissuesandlineages.
![Page 62: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/62.jpg)
WorkinginConsortia
![Page 63: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/63.jpg)
WorkingwithData
• GettingRawData
• Workingwiththedatafromdifferent
consortiasimultaneously:differentQCs,
differentdataanalysispipeline
• Versionsoftoolsmissedoroutdated/
unsupportedtools–failureofreplication!
![Page 64: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/64.jpg)
WorkinginConsortiaI
• WhenyourServergetsdownorallyour
datawereaccidentallyremoved
• Deadlines–add3-6monthstoexpected
date!
• Communication:teleconferences
• Passwordsrenewal,permissionstoaccess
• Efficientdatasharing–speed,reliability,
confidentiality
![Page 65: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/65.jpg)
WorkinginConsortiaII
• Differentnamingofthesamesamplesindifferentworkinggroups/labs
• Wrong/MissingIdentifiers(egwrongcancertypeorpopulation)–case:normalandsomaticwereactuallyswapped
• Thesame,butfromclinicians
• Differentlabs-differentlibrarypreparation(egcoveragedepthsafterPCR-freeandPCR-basedWGS)
• Severaltoolscanbeusedfortheanalysis–establishmentofthebesttoolorgenerationofjointcallset
• Multipleblacklistoroutlierlists(everylab/grouphasitsownandtheydonotcompletelyoverlap)
![Page 66: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/66.jpg)
WorkinginConsortiaIII
• UnbalancedPopulationStructure
• Mixofdifferenteffects(egCancervs.
Population)
• IsyourGermlinereallyGermline?
![Page 67: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/67.jpg)
SlidefromAgENCODE,EwanBirney
![Page 68: Standing on the shoulders of giants, German Demidov, …bioinformaticsinstitute.ru/sites/default/files/demidov... · 2020. 8. 31. · 1061–1073 (28 October 2010) > Phase 1: An integrated](https://reader035.vdocuments.site/reader035/viewer/2022071420/6118cdbc51bffc430d6e692f/html5/thumbnails/68.jpg)
Спасибозавнимание!